Introduction: Most of the data on metastatic breast cancer (MBC) originate from hospital-based studies or controlled trials involving specific populations and controlled treatments. In this respect, few population-based studies have analyzed the profile of MBC in low- and middle-income countries. Objective: To describe the epidemiological profile of women with de novo MBC using data from a population-based cancer registry (PBCR). Methods: An ecological study conducted in a PBCR in Goiânia, Brazil, for the 1995–2011 period. Women with MBC at diagnosis were included and the standardized incidence rate and annual percent change (APC) over the period were calculated. The women’s clinical and demographic characteristics and data on diagnosis and treatment were analyzed. Results: Overall, 5,289 cases of breast cancer were registered in the Goiânia PBCR, 277 (5.2%) at metastatic stage. The adjusted incidence was 8.9/100,000 in 1995 and 6.04/100,000 in 2011 (APC: 1.1; p=0.6). Most of the patients (70.3%) were receiving care within the public healthcare system and the mean age at diagnosis was 54.7±14.5 years. Additional data for a subpopulation of 156 patients were identified at the city’s two main treatment centers. According to immunohistochemistry, 53 women (67.1%) had hormone receptor-positive cancer. Of these, 14.0% (6/43) received endocrine therapy as first-line systemic treatment and 48.5% (17/35) as second-line treatment. A comparison of clinical data between the 1995–2003 and 2004–2011 periods revealed no significant differences in age, histological grade, locoregional staging, the presence of symptoms at diagnosis, or in treatment. Conclusion: This study population of women with MBC consisted predominantly of locally advanced tumors and the luminal-like subtype. The incidence rate of MBC in Goiânia did not change over the 17-year period. Most cases received chemotherapy as first-line systemic treatment irrespective of the tumor phenotype.
The KEYNOTE-522 regimen is the standard of care for stage II-III triple-negative breast cancer (TNBC). However, older patients were underrepresented in the pivotal trial. We evaluated the effectiveness and safety of this regimen in patients aged ≥65 years enrolled in the Neo-Real/GBECAM-0123 multicenter real-world study conducted across institutions in Brazil and Argentina. Among 724 patients, 80 (11%) were aged ≥65 years and presented distinct baseline characteristics, including lower frequencies of grade 3 tumors, Ki67 ≥ 50%, and germline BRCA1/2 mutations, alongside a higher prevalence of impaired performance status. The pathologic complete response (pCR) rate in older patients was 54.9% in comparison with 64.5% in younger patients, although age was not independently associated with pCR in multivariable analysis, including other relevant baseline variables. Older patients experienced a significantly higher toxicity burden, with increased rates of treatment discontinuation, dose reductions, treatment delays, hospitalizations, and grade ≥3 neutropenia. Taken together, these data indicate that older patients with TNBC harbor distinct biological and clinical features with numerically lower pCR rates, and that the increased toxicity burden underscores the need for personalized treatment strategies and dedicated research in this population.
Special histological types (SHT) of triple-negative breast cancer (TNBC) exhibit distinct biological behavior and treatment responses. However, due to their rarity, patients with SHT are underrepresented in clinical trials. We aimed to evaluate the effectiveness of pembrolizumab (P) combined with neoadjuvant chemotherapy (NCT) in patients with SHT of TNBC. We analyzed data from patients with TNBC and SHT enrolled in the Neo-Real/GBECAM-0123 study—a multicenter, real-world study including patients treated with neoadjuvant P+NCT across ten cancer centers since July 2020. Effectiveness outcomes included pathologic complete response (pCR) and event-free survival (EFS). Of the 727 patients included to date in the Neo-REAL study, 646 (88.9%) had TNBC of no special type (NST), 51 (7%) SHT, 4 (0.6%) undifferentiated, and 26 (3.6%) unknown histology. Among the SHT group, 20 metaplastic, 16 lobular, and 15 other subtypes (9 apocrine, 3 micropapillary, 2 neuroendocrine, and 1 medullary). Patients with lobular, metaplastic, and other SHT tumors were older than those with NST (median ages: 58, 51, 49, and 44 years, respectively; p = 0.001). Grade 3 tumors were more frequent in NST (76%) and metaplastic (84%) subtypes than in lobular (50%) and other SHT tumors (50%) (p = 0.019). A high Ki-67 index (≥50%) was also more common in NST tumors (76%) compared to metaplastic (52%), lobular (53%), and other SHT tumors (36%) (p < 0.001). Tumor stage distribution was similar across groups. Disease progression during P+NCT was significantly higher in the metaplastic group (33%) compared to NST (3%) and lobular tumors (0%) (p = 0.001). However, all but one patient with progression in the metaplastic group underwent surgery. pCR and EFS rates are presented in the Table. pCR rates were markedly lower in metaplastic tumors compared to NST and lobular subtypes. With a median follow-up of 22 months, 83 events of disease recurrence or death were recorded. Lobular and metaplastic tumors were associated with significantly lower 2-year EFS compared to NST. These differences remained significant in a multivariable Cox regression including tumor grade and stage. Patients with SHT of TNBC had worse outcomes with neoadjuvant pembrolizumab plus chemotherapy compared to those with NST tumors. Metaplastic carcinoma was associated with lower pCR and a trend tower lower EFS rates. Although lobular carcinoma had pCR rates similar to NST, an unfavorable EFS was also observed in this group. These results underscore the urgent need for developing new tailored therapeutic strategies for these rare and aggressive subtypes of TNBC. R. Barroso-Sousa, L. Testa, P. Mandó, M. C. Tavares, N. C. Nunes, G. Cordoba, F. Waisberg, F. C. Balint, I. M. de Sousa, M. O. Andrade, M. C. Gouveia, F. Madasi, J. Bines, R. P. Ferreira, D. D. Rosa, C. L. Santos, M. R. Monteiro, Z. S. de Souza, D. Assad-Suzuki, C. dos Anjos, D. M. Gagliato, A. U. Gomes, B. M. Zucchetti, A. Ferrari, M. L. de Brito, M. F. Monteiro, P. A. Signorini, N. J. Gomes, C. Gallina, S. Sanches, P. M. Hoff, M. Estevez-Diz, R. C. Bonadio. Rare but Resistant: Neoadjuvant Chemoimmunotherapy in Special Histological Subtypes of Triple-Negative Breast Cancer — Insights from the Neo-Real/GBECAM-0123 Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-04.
Background Talquetamab, a bispecific antibody targeting GPRC5D and CD3, has led to durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma in phase 1-2 trials, with a limited effect on normal B cells. Methods In a phase 3 trial, we randomly assigned patients with relapsed or refractory multiple myeloma who had previously received at least one line of therapy to receive talquetamab plus daratumumab and pomalidomide (Tal-DP), talquetamab plus daratumumab (Tal-D), or daratumumab plus pomalidomide and dexamethasone (DPd). The primary end point was progression-free survival as assessed by an independent review committee. Key secondary end points were overall response, complete response or better (complete or stringent complete response), measurable residual disease-negative complete response, and overall survival. Results A total of 287, 287, and 290 patients were assigned to the Tal-DP, Tal-D, and DPd groups, respectively. At the interim analysis (median follow-up, 24.6 months), progression-free survival was significantly longer with Tal-DP and Tal-D than with DPd (24-month estimate, 81.3% and 77.6% vs. 51.2%; hazard ratio for disease progression or death, Tal-DP vs. DPd, 0.28 [95% confidence interval {CI}, 0.20 to 0.40], and Tal-D vs. DPd, 0.33 [95% CI, 0.24 to 0.46]; P<0.001 for both comparisons). The overall response was higher with Tal-DP and Tal-D than with DPd (88.2% and 88.5% vs. 77.6%), as was complete response or better (71.1% and 69.0% vs. 34.5%) and measurable residual disease-negative complete response (52.3% and 46.3% vs. 15.9%) (P<0.001 for all comparisons). Overall survival at 24 months was 89.2% with Tal-DP, 87.9% with Tal-D, and 79.1% with DPd (hazard ratio for death, Tal-DP vs. DPd, 0.47 [95% CI, 0.30 to 0.73], and Tal-D vs. DPd, 0.51 [95% CI, 0.33 to 0.78]). Serious adverse events occurred in 63.0%, 52.6%, and 53.7% of the patients in the Tal-DP, Tal-D, and DPd groups, respectively; fatal adverse events occurred in 1.8%, 4.0%, and 4.6%. Conclusions Among patients with relapsed or refractory multiple myeloma who had previously received at least one line of therapy, both Tal-DP and Tal-D led to significantly longer progression-free survival than DPd. (Funded by Johnson & Johnson; MonumenTAL-3 ClinicalTrials.gov number, NCT05455320.)
Generative artificial intelligence represents a fascinating, disruptive force in cytopathology. Anecdotal experience with the commercially available ChatGPT confirms both its appeal and limitations.
